China
Africa
Explore chapters and articles related to this topic
Pathogenesis of Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Divya B. Reddy, Jerrold J. Ellner
More recently, an abundant lipoglycan of the mycobacterial cell wall, lipoarabinomannan (LAM), has been ascribed to virulence function(s).24 LAM, being a key immunomodulator, counteracts interferon (IFN)-γ-induced macrophage activation, arrests phagosomal maturation in infected macrophages, reduces phagocytosis, and blocks induction of cellular genes. By modulating the cytokine milieu toward one of deactivations, LAM may allow the persistence of MTB within tissues.22,27 Gaur et al. showed that LprG, a cell envelope lipoprotein, is essential for normal surface expression of LAM and its functions.28
Bacteria-Derived Alternatives to Live Mycobacterium bovis Bacillus Calmette–Guerin for Nonmuscle Invasive Bladder Cancer Treatment
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
Esther Julián, Estela Noguera-Ortega
The understanding of the repertoire of antigenic compounds and their location in each species of mycobacteria is relevant not only because of their possible immunostimulatory effect but also because some of them could interfere with the interaction of mycobacteria with host cells or mask the effect of the other antigenic molecules. Different examples illustrate these two aspects. Regarding the immunostimulatory effect of each strain/species, lipoarabinomannan (LAM) with mannose caps (Man-LAM) is present in pathogenic species and binds to the MR or DC-SIGN receptor, reducing IL-2 and TNF secretion and increasing the secretion of anti-inflammatory cytokines [127, 128]; fast-growing nonpathogenic mycobacteria have terminal arabinose (Ara-LAM) or phosphatidylinositol (PILAM) LAM, which binds to TLR2, triggering a robust immunostimulatory effect with increased IL-12 and TNF production [129–131]. Another example is the case of BCG strains. Deletions and insertions in the genome of BCG after the serial passage of BCG in each laboratory after the initial seed distribution from the Pasteur Institute have resulted in differences in the antigenic pattern (Table 4.1) and consequently in the immunological activities. Even considering members of the same species, BCG strains differ in the presence of phenol glycolipid (PGL), phthiocerol dimycocerosates (PDIM), or MPT64 or in mycolic acid composition [6, 111, 132–135]). All these antigens are related to the BCG-induced immune response [132, 133].
Mycobacterium tuberculosis – The Organism
Published in Peter D O Davies, Stephen B Gordon, Geraint Davies, Clinical Tuberculosis, 2014
Being intracellular pathogens, members of the M. tuberculosis complex have mechanisms facilitating their phagocytosis by macrophages and, in common with other bacteria, this may involve complement activation and mannose binding. A key mechanism of survival within macrophages is the ability of the bacilli to inhibit phagosome maturation and to block phagosome–lysosome fusion [90]. These processes inhibit the acidification of phagosomes and the generation of various reactive oxygen and nitrogen molecules involved in killing of the bacilli [91]. Mannose-capped lipoarabinomannan (ManLAM) of M. tuberculosis facilitates entry into macrophages by binding to mannose receptors and also inhibits phagosomal activity [60].
Effect of mycobacterial proteins that target mitochondria on the alveolar macrophages activation during Mycobacterium tuberculosis infection
Published in Experimental Lung Research, 2022
Iris Selene Paredes-González, Omar Emiliano Aparicio-Trejo, Octavio Ramos-Espinosa, Manuel Othoniel López-Torres, Milena Maya-Hoyos, Monserrat Mendoza-Trujillo, Alejandra Barrera-Rosales, Dulce Mata-Espinosa, Juan Carlos León-Contreras, José Pedraza-Chaverri, Clara Espitia, Rogelio Hernández-Pando
The mitochondria’s role in the metabolism during bacterial infection is also critical, because it may determine the fate of infected MQs, an aspect that is not yet thoroughly studied. Some secreted proteins from Mtb, such as P27 (Rv1411c, LprG) and PE_PGRS33 (Rv1818c), have a signal sequence that targets MQ mitochondria.7,8 P27, a lipoarabinomannan carrier lipoprotein, is present in the mycobacterial membrane and cell wall. This protein is part of the P27-P55 operon that contributes to the extracellular transport of toxic compounds9 and participates in lipid metabolism and fatty acid traffic.10 Therefore, P27 has a significant importance in the function and integrity of the mycobacterial cell wall. Similarly, PE_PGRS33 is also located in the bacterial cell wall and facilitates the entry of the bacilli to MQs.11,12 PE_PGRS33 is expressed in different strains of Mtb and under diverse growth conditions, suggesting that it contributes to essential bacterial functions.13 This protein is highly expressed in samples from subjects with active pulmonary TB,14 suggesting its association with disease progression and may be considered as a biomarker in the future.
Polyamine biomarkers as indicators of human disease
Published in Biomarkers, 2021
Mohsin Amin, Shiying Tang, Liliana Shalamanova, Rebecca L. Taylor, Stephen Wylie, Badr M. Abdullah, Kathryn A. Whitehead
The use of biomarkers where typical diagnosis methods are insufficient, expensive and/or time-consuming, may result in the most successful application for the use of biomarkers (Lubell and Althaus 2017). Since biomarkers are able to provide a clinician with valuable diagnostic and prognostic information regarding the current health status of an individual, their applicability in various bacterially driven diseases is of major importance (Tang et al.2017, Gomez et al.2019). For example, tuberculosis (TB), is a communicable infectious disease that is known for having a long incubation time (2–8 weeks), resulting in a severely delayed confirmation diagnosis. This is due to the detection methods relying on the bacteria being cultured to provide a positive confirmation. However, new biomarkers in the form of lipoarabinomannan, a virulence factor and glycolipid of the cell wall of the causative agent of TB (Mycobacterium tuberculosis) has shown good specificity to determine the presence of TB in the blood sputum and urine, without the use of traditional bacterial cultures (Wallis et al.2010, Goletti et al.2016, Correia-Neves et al.2019). This example demonstrates the effectiveness of the potential of new biomarkers as rapid detection alternatives. The use of such systems has the possibility to reduce diagnosis times whilst maintaining comparable levels of diagnostic accuracy to that of traditional techniques.
The use of immunotherapy for the treatment of tuberculosis
Published in Expert Review of Respiratory Medicine, 2018
Octavio Ramos-Espinosa, León Islas-Weinstein, Marco Polo Peralta-Álvarez, Manuel Othoniel López-Torres, Rogelio Hernández-Pando
Lipoarabinomannan (LAM) is the most prominent antigen in the bacterial surface. As a consequence, in active disease, a high number of Abs against this glycolipid are found. LAM-specific mAbs SMITB14 and its F(ab’)2 fragment have been evaluated in a BALB/c model of TB. Intravenous administration of SMITB14 prior to infection, or simultaneously with Mtb, induced a bacterial burden reduction in lungs and spleen, reduced weight loss, and improved survival rates in comparison to untreated mice [82]. It is highly probable that the mechanism that confers protection in this study is due to the specific binding of mAbs to bacteria, thus facilitating opsonization and early elimination by phagocytic cells.